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    Suppression of Slit2/Robo1 mediated HUVEC migration by Robo4.
    Biochem Biophys Res Commun 2016 Jan 20;469(4):797-802. Epub 2015 Dec 20.
    Department of Quantitative Biology and Medicine, Research Center for Advanced Science and Technology, The University of Tokyo, Tokyo, Japan. Electronic address:
    Slit proteins and their receptors, the Roundabout (Robo) family, are known to have a pivotal role in the vascular system. Slit2/Robo1 regulates the migration of human umbilical vein endothelial cells (HUVECs) and tumor-associated endothelial cells. Robo4, the endothelial-specific Robo, is also considered to be involved in vascular cell migration. However, the Slit/Robo signaling pathway is still unclear. Using a Boyden chamber assay, we found that Slit2 induces the migration of HUVECs under a Robo4 knockdown condition. This effect disappeared in Robo1 knockdown cells. The co-existence of the N-terminal extracellular portion of Robo1 blocked the Slit2-evoked migration of HUVECs, while that of Robo4 caused no effect. These results show that the Slit2 signal is transduced through Robo1, while the negative regulation of Robo4 is an intracellular event. Targeted proteomics using an anti-Robo1 monoclonal antibody identified CdGAP, an adhesion-localized Rac1-and Cdc42-specific GTPase activating protein, as a candidate for Slit2/Robo1 signaling. Robo1 and CdGAP were co-immunoprecipitated from CHO cells co-transfected with Robo1 and CdGAP genes. These results suggest that Slit2/Robo1 binding exerts an effect on cell migration, which is negatively regulated by Robo4, and Robo1 may function by interacting with CdGAP in HUVECs.

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    Human placental multipotent mesenchymal stromal cells modulate placenta angiogenesis through Slit2-Robo signaling.
    Cell Adh Migr 2016 Mar 8;10(1-2):66-76. Epub 2016 Jan 8.
    a Department of Medical Research , MacKay Memorial Hospital , Taipei , Taiwan.
    The objective of this study was to investigate whether human placental multipotent mesenchymal stromal cell (hPMSC)-derived Slit2 and endothelial cell Roundabout (Robo) receptors are involved in placental angiogenesis. The hPMSC-conditioned medium and human umbilical vein endothelial cells were studied for Slit2 and Robo receptor expression by immunoassay and RT-PCR. The effect of the conditioned medium of hPMSCs with or without Slit2 depletion on endothelial cells was investigated by in vitro angiogenesis using growth factor-reduced Matrigel. Read More
    Active involvement of Robo1 and Robo4 in filopodia formation and endothelial cell motility mediated via WASP and other actin nucleation-promoting factors.
    FASEB J 2009 Feb 23;23(2):513-22. Epub 2008 Oct 23.
    Molecular Angiogenesis Group, Cancer Research UK, Institute of Molecular Medicine, University of Oxford, Oxford, UK.
    This study aimed to further elucidate the function of Roundabout proteins in endothelium. We show that both Robo1 and Robo4 are present in human umbilical vein endothelial cells (HUVECs) and have knocked expression down using small interfering RNA (siRNA) technology. Roundabout knockout endothelial cells were then studied in a variety of in vitro assays. Read More
    Potential anti-angiogenic role of Slit2 in corneal neovascularization.
    Exp Eye Res 2010 Jun 16;90(6):742-9. Epub 2010 Mar 16.
    Department of Ophthalmology, Wuhan Union Hospital, Tongji Medical College of Huazhong University of Science & Technology, 1277 Jiefang Avenue, Wuhan 430022, Hubei Province, China.
    Slits are large secreted proteins critical for axon guidance and neuronal precursor cell migration in nervous system. Evidence suggests that classical neuronal guidance cues also regulate vascular development. Our objective was to investigate whether neuronal guidance cue Slit2 and Roundabout (Robo) receptors are involved in corneal neovascularization (NV). Read More
    Silencing of directional migration in roundabout4 knockdown endothelial cells.
    BMC Cell Biol 2008 Nov 3;9:61. Epub 2008 Nov 3.
    Genome Technology Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, USA.
    Background: Roundabouts are axon guidance molecules that have recently been identified to play a role in vascular guidance as well. In this study, we have investigated gene knockdown analysis of endothelial Robos, in particular roundabout 4 (robo4), the predominant Robo in endothelial cells using small interfering RNA technology in vitro.

    Results: Robo1 and Robo4 knockdown cells display distinct activity in endothelial cell migration assay. Read More